The cell surface metalloprotease/disintegrin Kuzbanian is required for axonal extension in Drosophila

It has long been suspected that proteolytic activity associated with advancing growth cones may be required for axon extension. We have isolated mutations in thekuzbanian (kuz ) gene, which is expressed in the nervous system and encodes a putative zinc metalloprotease with a disintegrin domain.Drosophila embryos with loss-of-function mutations inkuz have dramatic defects in the development of central nervous system axon pathways, with many axons stalling and failing to extend through the nerve cord. This phenotype is rescued by panneural expression ofkuz mRNA in the embryo. These results show that the Kuz metalloprotease is required for axon extension, suggesting a requirement for proteolytic activity at the growth cone surface.